Abstract

In order to investigate the basic physiological mechanisms of pain and the anti-nociceptive effects of analgesics, development of pain assays in mice is critical due to the advances of genetic manipulation techniques. The von Frey hairs/Semmes-Weinstein monofilaments test (von Frey test) has long been applied to examine mechanical nociception in mice. Though the von Frey test is a well-established and standardized method, it is inappropriate to assess a rapid change in the nociceptive threshold because voluntary resting/sleeping states are necessary to examine the response. In this study, we assessed the effectiveness of calibrated forceps to determine the mechanical nociceptive threshold in mice. Repeated daily measurements of the threshold over 5 days indicated that the device obtained stable and reliable values. Furthermore, repeated measurements with 5 minute intervals revealed that the device detected the rapid change of the threshold induced by remifentanil, a short-acting μ-receptor agonist. These results indicate that the calibrated forceps are well-suited for measuring the mechanical nociceptive threshold in mice, and are useful in assessing the effects of short-acting analgesics on mechanical nociception.

Highlights

  • In clinical anesthesia, short-acting analgesics are gaining importance recently because they allow for quick and on-demand control of the depth of anesthesia and enable swift recovery

  • The basic research of short-acting analgesics for mechanical pain was only limited and the evaluation was mainly performed for thermal pain because the established protocols for assessing the mechanical nociception has low time resolution (>30 minutes)

  • We originally planned to measure the nociceptive threshold in the hind paws of mice

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Summary

Introduction

Short-acting analgesics are gaining importance recently because they allow for quick and on-demand control of the depth of anesthesia and enable swift recovery. The basic research of short-acting analgesics for mechanical pain was only limited and the evaluation was mainly performed for thermal pain because the established protocols for assessing the mechanical nociception has low time resolution (>30 minutes). The new techniques for mechanical nociception with high time resolution (< 5minutes) has been required. When investigating the mechanisms of nociception and the effects of anti-nociceptive drugs pre-clinically, some of the most common techniques include determining the threshold and measuring the duration of behavioral responses to nociceptive stimulation in rodents [1]. Nociceptive tests have long been performed mainly in rat. The mouse models of PLOS ONE | DOI:10.1371/journal.pone.0172461. The mouse models of PLOS ONE | DOI:10.1371/journal.pone.0172461 February 17, 2017

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